CN1070484C - 促使血清脂质减少的1,4－苯并噻吖庚因－1,1－二氧化物 - Google Patents

促使血清脂质减少的1,4－苯并噻吖庚因－1,1－二氧化物 Download PDF

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Publication number: CN1070484C
Authority: CN; China
Prior art keywords: compound; formula; alkyl; group; compounds
Prior art date: 1997-03-14
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CN98108046A

Other languages

English (en)

Chinese (zh)

Other versions

CN1194979A (zh

Inventor

A·恩森

E·法尔克

H·格罗姆比克

S·斯坦格林

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Hoechst AG

Original Assignee

Hoechst AG

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-03-14

Filing date

1998-03-13

Publication date

2001-09-05

1998-03-13 Application filed by Hoechst AG filed Critical Hoechst AG

1998-10-07 Publication of CN1194979A publication Critical patent/CN1194979A/zh

2001-09-05 Application granted granted Critical

2001-09-05 Publication of CN1070484C publication Critical patent/CN1070484C/zh

2018-03-13 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

230000000055 hyoplipidemic effect Effects 0.000 title abstract 3
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/007—Vector systems having a special element relevant for transcription cell cycle specific enhancer/promoter combination
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/80—Vector systems having a special element relevant for transcription from vertebrates
- C12N2830/85—Vector systems having a special element relevant for transcription from vertebrates mammalian
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
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Genetics & Genomics (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
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Pharmacology & Pharmacy (AREA)
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Cardiology (AREA)
Emergency Medicine (AREA)
Vascular Medicine (AREA)
Gastroenterology & Hepatology (AREA)
Urology & Nephrology (AREA)
Heart & Thoracic Surgery (AREA)
Endocrinology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Plural Heterocyclic Compounds (AREA)

CN98108046A 1997-03-14 1998-03-13 促使血清脂质减少的1,4－苯并噻吖庚因－1,1－二氧化物 Expired - Fee Related CN1070484C (zh)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP97104348		1997-03-14
EP97104348.4		1997-03-14

Publications (2)

Publication Number	Publication Date
CN1194979A CN1194979A (zh)	1998-10-07
CN1070484C true CN1070484C (zh)	2001-09-05

Family

ID=8226598

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Application Number	Title	Priority Date	Filing Date
CN98108046A Expired - Fee Related CN1070484C (zh)	1997-03-14	1998-03-13	促使血清脂质减少的1,4－苯并噻吖庚因－1,1－二氧化物

Country Status (23)

Country	Link
US (2)	US6020330A (es)
EP (1)	EP0864582B1 (es)
JP (1)	JP3282998B2 (es)
KR (1)	KR19980080223A (es)
CN (1)	CN1070484C (es)
AR (1)	AR011189A1 (es)
AT (1)	ATE242258T1 (es)
AU (1)	AU731575B2 (es)
BR (1)	BR9801126A (es)
CA (1)	CA2231971C (es)
CZ (1)	CZ75998A3 (es)
DE (1)	DE69815180T2 (es)
DK (1)	DK0864582T3 (es)
ES (1)	ES2198613T3 (es)
HU (1)	HUP9800541A3 (es)
ID (1)	ID20053A (es)
IL (1)	IL123648A (es)
NZ (1)	NZ329932A (es)
PL (1)	PL325363A1 (es)
PT (1)	PT864582E (es)
RU (1)	RU2179977C2 (es)
TR (1)	TR199800444A2 (es)
ZA (1)	ZA982140B (es)

Families Citing this family (89)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6642268B2 (en)	1994-09-13	2003-11-04	G.D. Searle & Co.	Combination therapy employing ileal bile acid transport inhibiting benzothipines and HMG Co-A reductase inhibitors
US6268392B1 (en)	1994-09-13	2001-07-31	G. D. Searle & Co.	Combination therapy employing ileal bile acid transport inhibiting benzothiepines and HMG Co-A reductase inhibitors
US6262277B1 (en) *	1994-09-13	2001-07-17	G.D. Searle And Company	Intermediates and processes for the preparation of benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake
DE69815180T2 (de) *	1997-03-14	2004-04-29	Aventis Pharma Deutschland Gmbh	Hypolipidemische 1,4-Benzothiazepin-1,1-dioxide
KR20010102965A (ko)	1998-12-23	2001-11-17	윌리암스 로저 에이	심장혈관의 징후에 대한 회장 담즙산 수송 저해제 및담즙산 격리제의 병용
JP2002533413A (ja)	1998-12-23	2002-10-08	ジー．ディー．サールエルエルシー	心臓血管に適用するための回腸胆汁酸輸送阻害剤およびフィブリン酸誘導体の組み合わせ
DK1140185T3 (da)	1998-12-23	2003-09-29	Searle Llc	Kombinationer af cholesterylestertransferhæmmere og galdesyre kompleksdannende forbindelser til hjertekar indikationer
KR20010099937A (ko)	1998-12-23	2001-11-09	윌리암스 로저 에이	심혈관 징후용 콜레스테릴 에스테르 전달 단백질 억제제및 피브르산 유도체의 조합물
EA200100704A1 (ru) *	1998-12-23	2002-02-28	Джи.Ди.Сирл Ллс	Комбинация для применения по сердечно-сосудистым показаниям
ATE242007T1 (de)	1998-12-23	2003-06-15	Searle Llc	Kombinationen von cholesteryl ester transfer protein inhibitoren und nicotinsäure derivaten für kardiovaskuläre indikationen
US6462091B1 (en)	1998-12-23	2002-10-08	G.D. Searle & Co.	Combinations of cholesteryl ester transfer protein inhibitors and HMG coA reductase inhibitors for cardiovascular indications
EP1342475A1 (en)	1998-12-23	2003-09-10	G.D. Searle LLC.	Combinations of ileal bile acid transport inhibitors and cholesteryl ester transfer protein inhibitors for cardiovascular indications
DE19916108C1 (de) *	1999-04-09	2001-01-11	Aventis Pharma Gmbh	Mit Zuckerresten substituierte 1,4-Benzothiazepin-1,1-dioxidderivate, Verfahren zu deren Herstellung und deren Verwendung
GB9914745D0 (en) *	1999-06-24	1999-08-25	Knoll Ag	Therapeutic agents
SE0000772D0 (sv)	2000-03-08	2000-03-08	Astrazeneca Ab	Chemical compounds
AU2001240115A1 (en)	2000-03-10	2001-09-24	Pharmacia Corporation	Method for the preparation of tetrahydrobenzothiepines
AU2001247331A1 (en) *	2000-03-10	2001-09-24	Pharmacia Corporation	Combination therapy for the prophylaxis and treatment of hyperlipidemic conditions and disorders
US20020183307A1 (en) *	2000-07-26	2002-12-05	Tremont Samuel J.	Novel 1,4-benzothiazephine and 1,5-benzothiazepine compounds as inhibitors of apical sodium co-dependent bile acid transport and taurocholate uptake
EG26979A (en)	2000-12-21	2015-03-01	Astrazeneca Ab	Chemical compounds
US20040077625A1 (en) *	2001-07-25	2004-04-22	Tremont Samuel J.	Novel 1,4-benzothiazepine and 1,5-benzothiazepine compounds as inhibitors of apical sodium codependent bile acid transport abd taurocholate uptake
GB0121337D0 (en)	2001-09-04	2001-10-24	Astrazeneca Ab	Chemical compounds
GB0121622D0 (en)	2001-09-07	2001-10-31	Astrazeneca Ab	Chemical compounds
GB0121621D0 (en)	2001-09-07	2001-10-31	Astrazeneca Ab	Chemical compounds
CN1582151A (zh)	2001-09-08	2005-02-16	阿斯特拉曾尼卡有限公司	用于治疗高脂血症、具有回肠胆汁酸转运(ibat)抑制活性的苯并硫氮杂䓬和苯并硫杂二氮杂䓬衍生物
JP2005518347A (ja) *	2001-11-02	2005-06-23	ジー．ディー．サールエルエルシー	頂端ナトリウム共依存性胆汁酸輸送（ａｓｂｔ）およびタウロコール酸塩取り込みの阻害剤としての新規一および二フッ化ベンゾチエピン化合物
EP1465885A4 (en)	2002-01-17	2005-04-27	Pharmacia Corp	NOVEL ALKYL / ARYL HYDROXY OR CETOTHIEPINE COMPOUNDS AS INHIBITORS OF BILIARY ACID TRANSPORT OF THE ILEAL TYPE AND ABSORPTION OF TAUROCHOLATE
GB0201850D0 (en) *	2002-01-26	2002-03-13	Astrazeneca Ab	Therapeutic treatment
GB0209467D0 (en)	2002-04-25	2002-06-05	Astrazeneca Ab	Chemical compounds
GB0213669D0 (en)	2002-06-14	2002-07-24	Astrazeneca Ab	Chemical compounds
US7312208B2 (en)	2002-08-28	2007-12-25	Asahi Kasei Pharma Corporation	Quaternary ammonium compounds
GB0304194D0 (en) *	2003-02-25	2003-03-26	Astrazeneca Ab	Chemical compounds
GB0307918D0 (en)	2003-04-05	2003-05-14	Astrazeneca Ab	Therapeutic use
KR20070026392A (ko)	2004-02-27	2007-03-08	아사히 가세이 파마 가부시키가이샤	신규 벤조티아제핀 및 벤조티에핀 화합물
DE102005033099A1 (de) *	2005-07-15	2007-01-18	Sanofi-Aventis Deutschland Gmbh	Neues 1,4-Benzothiazepin-1,1-Dioxidderivat mit verbesserten Eigenschaften, Verfahren zu dessen Herstellung, diese Verbindung enthaltende Arzneimittel und dessen Verwendung
CN102316872B (zh) *	2008-11-26	2016-12-21	萨蒂奥根制药公司	治疗肥胖症和糖尿病的胆汁酸再循环抑制剂
EP3593802A3 (en)	2010-05-26	2020-03-25	Satiogen Pharmaceuticals, Inc.	Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions
BR112013010157B1 (pt)	2010-11-04	2020-02-04	Albireo Ab	iinibidores do ibat, seus usos, e composição e combinações farmacêuticas
US20130236541A1 (en)	2010-11-08	2013-09-12	Albireo Ab	Pharmaceutical combination comprising an ibat inhibitor and a bile acid binder
BR112014010223B8 (pt)	2011-10-28	2021-02-23	Lumena Pharmaceuticals Llc	uso de uma composição compreendendo inibidores de reciclagem de ácido de bílis e forma de dosagem pediátrica
AU2012328453B2 (en)	2011-10-28	2017-05-04	Shire Human Genetic Therapies, Inc.	Bile acid recycling inhibitors for treatment of hypercholemia and cholestatic liver disease
BR112015023646A2 (pt)	2013-03-15	2017-07-18	Lumena Pharmaceuticals Inc	inibidores de ácidos biliares de reciclagem para tratamento de colangite esclerosante primária e doença inflamatória do intestino
AU2014229050A1 (en)	2013-03-15	2015-10-22	Lumena Pharmaceuticals Llc	Bile acid recycling inhibitors for treatment of Barrett's esophagus and gastroesophageal reflux disease
JO3301B1 (ar)	2013-04-26	2018-09-16	Albireo Ab	تعديلات بلورية على إيلوبيكسيبات
KR20220082931A (ko)	2014-06-25	2022-06-17	이에이 파마 가부시키가이샤	고형 제제 및 그의 착색 방지 또는 착색 감소 방법
EP3012252A1 (en)	2014-10-24	2016-04-27	Ferring BV	Crystal modifications of elobixibat
RU2730524C2 (ru) *	2015-03-02	2020-08-24	Апейрон Биолоджикс Аг	Бициклические тетрагидротиазепиновые производные, полезные для лечения неопластических и/или инфекционных заболеваний
RU2750944C2 (ru)	2016-02-09	2021-07-06	Альбирео Аб	Пероральный состав холестирамина и его применение
US10786529B2 (en)	2016-02-09	2020-09-29	Albireo Ab	Oral cholestyramine formulation and use thereof
EP3413878B1 (en)	2016-02-09	2021-04-14	Albireo AB	Oral cholestyramine formulation and use thereof
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US10441605B2 (en)	2016-02-09	2019-10-15	Albireo Ab	Oral cholestyramine formulation and use thereof
CA3071182A1 (en)	2017-08-09	2019-02-14	Albireo Ab	Cholestyramine pellets, oral cholestyramine formulations and use thereof
EP3664781A1 (en)	2017-08-09	2020-06-17	Albireo AB	Cholestyramine granules, oral cholestyramine formulations and use thereof
US10793534B2 (en)	2018-06-05	2020-10-06	Albireo Ab	Benzothia(di)azepine compounds and their use as bile acid modulators
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1993016055A1 (en) *	1992-02-17	1993-08-19	The Wellcome Foundation Limited	Hypolipidaemic benzothiazepine compounds
WO1994018184A1 (en) *	1993-02-15	1994-08-18	The Wellcome Foundation Limited	Hypolipidaemic compounds
WO1994018183A1 (en) *	1993-02-15	1994-08-18	The Wellcome Foundation Limited	Hypolipidaemic condensed 1,4-thiazepines

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BR9307387A (pt) *	1992-11-09	1999-08-31	Boots Co Plc	Agentes terapêuticos
ZA956647B (en) *	1994-08-10	1997-02-10	Wellcome Found	Hypolipidaemic compounds.
DE69815180T2 (de) *	1997-03-14	2004-04-29	Aventis Pharma Deutschland Gmbh	Hypolipidemische 1,4-Benzothiazepin-1,1-dioxide

1998
- 1998-03-03 DE DE69815180T patent/DE69815180T2/de not_active Expired - Lifetime
- 1998-03-03 AT AT98103702T patent/ATE242258T1/de active
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- 1998-03-12 CA CA002231971A patent/CA2231971C/en not_active Expired - Fee Related
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- 1998-03-12 AU AU58349/98A patent/AU731575B2/en not_active Ceased
- 1998-03-12 CZ CZ98759A patent/CZ75998A3/cs unknown
- 1998-03-13 KR KR1019980008440A patent/KR19980080223A/ko not_active Ceased
- 1998-03-13 BR BR9801126A patent/BR9801126A/pt not_active IP Right Cessation
- 1998-03-13 CN CN98108046A patent/CN1070484C/zh not_active Expired - Fee Related
- 1998-03-13 JP JP06266598A patent/JP3282998B2/ja not_active Expired - Fee Related
- 1998-03-13 US US09/041,953 patent/US6020330A/en not_active Expired - Lifetime
- 1998-03-13 ZA ZA982140A patent/ZA982140B/xx unknown
- 1998-03-14 PL PL98325363A patent/PL325363A1/xx not_active Application Discontinuation
1999
- 1999-07-27 US US09/361,530 patent/US6114322A/en not_active Expired - Lifetime

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1993016055A1 (en) *	1992-02-17	1993-08-19	The Wellcome Foundation Limited	Hypolipidaemic benzothiazepine compounds
WO1994018184A1 (en) *	1993-02-15	1994-08-18	The Wellcome Foundation Limited	Hypolipidaemic compounds
WO1994018183A1 (en) *	1993-02-15	1994-08-18	The Wellcome Foundation Limited	Hypolipidaemic condensed 1,4-thiazepines

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Publication number	Publication date
CA2231971C (en)	2008-05-20
AU5834998A (en)	1998-09-17
ATE242258T1 (de)	2003-06-15
TR199800444A3 (tr)	1998-10-21
HU9800541D0 (en)	1998-05-28
JPH10279568A (ja)	1998-10-20
IL123648A0 (en)	1998-10-30
RU2179977C2 (ru)	2002-02-27
CA2231971A1 (en)	1998-09-14
HUP9800541A3 (en)	2000-08-28
ES2198613T3 (es)	2004-02-01
DK0864582T3 (da)	2003-09-29
US6114322A (en)	2000-09-05
EP0864582B1 (en)	2003-06-04
JP3282998B2 (ja)	2002-05-20
HUP9800541A1 (hu)	1999-06-28
US6020330A (en)	2000-02-01
TR199800444A2 (xx)	1998-10-21
CN1194979A (zh)	1998-10-07
DE69815180T2 (de)	2004-04-29
PL325363A1 (en)	1998-09-28
AR011189A1 (es)	2000-08-02
ID20053A (id)	1998-09-17
IL123648A (en)	2000-11-21
EP0864582A2 (en)	1998-09-16
AU731575B2 (en)	2001-04-05
DE69815180D1 (de)	2003-07-10
ZA982140B (en)	1998-09-14
PT864582E (pt)	2003-10-31
CZ75998A3 (cs)	1998-09-16
EP0864582A3 (en)	1998-10-21
BR9801126A (pt)	2000-03-21
NZ329932A (en)	1999-01-28
KR19980080223A (ko)	1998-11-25

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